Table 6.

Clinical trials on PRF derivatives for tendons repair.

End Use Destination	Hemocomponent/Experimental Groups	PRF Preparation Protocol	Characterization Parameters	Major Findings	Reference
Full-thickness rotator cuff tear	n = 20 patients (mean age = 57.6 years): Arthroscopic single-row rotator cuff repair + 2 autologous PRP, sutured into the repair site   n = 20 patients (mean age = 57.8 years; range = 44–69 years): Arthroscopic single-row rotator cuff repair	- Cascade autologous platelet system	Mean follow up and range: PRP, 28.3 (24–44) months; no PRP, 33 (24–44) months - MRI - Clinical outcome measures by ASES, Rowe, SANE, SST and Constant scores	- Retears: with PRP: 6 of 20 (30%); no PRP: 12 of 20 (60%) - Cuff tear size (no. healed): <3 cm, 7 of 14 (50%) no PRP; 12 of 14 (86%) with PRP. ≥3 cm, 1 of 6 (17%) no PRP; 2 of 6 (33%) with PRP - Significant clinical differences showing lower re-tear rates by MRI only with Rowe score	Barber et al., 2011 [104]
Arthroscopic rotator cuff repair	n = 43 patients (mean age = 55.5 years): Tear size (cm): small (<1); medium (1–3), PRFM   n = 45 patients (mean age = 55.2 years): Tear size (cm): small (<1), medium (1–3), no PRFM	- Blood collection in a tube with trisodium citrate and a thixotropic polyester separator gel - 1st centrifugation (1100 rpm, 6 min) - Transfer of the supernatant in a bottle containing calcium chloride (1.0 M) - 2nd centrifugation (4500 RCF, 25 min)	Follow up: 16 months - Clinical outcome by Constant scores - MRI	- Statistically significant improvement in both groups but any among groups - Difference in alterations of MRI signal intensity - Re-rupture in 10.5% patients of control group and 2.5% in PRFM group but any additional treatment occurred - No difference in tendon thickness or in size of the tendon footprint tendon thickness	Castricini et al., 2011 [107]
Arthroscopic rotator cuff repair	n = 16 patients (mean age = 65 ± 7 years): Tear size: 3.8 ± 1.1 cm, PRFM   n = 21 patients (mean age = 65 ± 9 years): Tear size: 3.9 ± 1.1 cm, no PRFM	- Blood collection in a tube with trisodium citrate - 1st centrifugation (1100 rpm, 6 min) - Transfer of supernatant into a second tube containing calcium chloride, which initiates the fibrin-clotting cascade - 2nd centrifugation (1450 rpm, 15 min) The Cascade Autologous Platelet System was used to prepare the PRFM	Mean follow-up: PRFM group, 13 ± 4 months; Untreated group, 27 ± 8 months   - Operative time - MRI - Clinical outcome scores by Constant, WORC, SANE, ASES, UCL	- Retear rates: statistically significantly higher in the PRFM group (56.2%) vs. controls (38.1%) - Functional outcome scores postoperatively: not significantly improved in PRFM vs. controls - Operative time (min): 152 ± 31 in PRFM group vs 161 ± 40 in control group - 2 infections in the PRFM group - The augmentation of at-risk rotator cuff tears with PRFM did not result in improved retear rates or functional outcome scores compared with controls	Bergeson et al., 2012 [106]
Full-thickness rotator cuff tear	n = 40 patients (mean age = 58.90 ± 9.86 years): Tear size (nr. of patients): small: 10; medium: 20; large: 10, PRFM treatment   n = 39 patients (mean age = 7.21 ± 9.42 years): Tear size (nr. of patients): small: 10; medium: 19; large: 10, No PRFM	- Cascade Membrane (Musculoskeletal Tissue Foundation, Edison, NJ, USA)	Follow-up: 6 weeks, 3 and 12 months - Power doppler ultrasound - Manual muscle testing ratio - Clinical outcome scores by ASES and l’Insalata - Strength measurements using a handheld dynamometer	- Intact repair in 24 of 36 (67%) in the PRFM group and 25 of 31 (81%) in the control group - No differences in tendon-to-bone healing - No demonstrable effect on tendon healing vascularity, manual muscle strength, or clinical rating scales by PRFM - Negative effect of PRFM on healing according to regression analysis	Rodeo et al., 2012 [109]
Arthroscopic rotator cuff repair	n = 30 patients (mean age = 59.67 ± 8.16 years): Tear size: 1.77 ± 0.84 cm, PRFM treatment (commercially available)   n = 30 patients (mean age = 64.50 ± 8.59 years): Tear size: 1.72 ± 1.18 cm, no PRFM	- Cascade Membrane (Musculoskeletal Tissue Foundation, Edison, NJ, USA)	Follow-up: 1 h, 3, 6, 9, and 12 weeks, 1 year - Operative time - VAS pain scores, ROM, SST, FF, ER, UCLA, ASES scores - Narcotic consumption - MRI	- No complications - Longer mean surgery time for the PRFM group than control group - No significant difference in VAS, ROM, SST, FF, ER or ASES scores or narcotic use - Similar UCLA scores in both groups at baseline but statistically significantly lower in the PRFM group at follow-up - No differences in MRI - No significant improvement in perioperative morbidity, structural integrity or clinical outcome in PRFM in early follow-up	Weber et al., 2013 [110]
Full-thickness rotator cuff tears	n = 20 patients (mean age = 55 years): Tear size: ≤3 cm in anteroposterior length, suture-bridging double-row repair + PRPFM   n = 20 patients (mean age = 57 years): Tear size: no greater than 3 cm in anteroposterior length, triple - loaded single row repair + PRPFM	- Cascade Membrane (Musculoskeletal Tissue Foundation, Edison, NJ, USA)	Mean follow-up and range: double-row group, 27 (12–46) months; single-row group, 28 (12–49) months - ASES, Rowe, SST, Constant, SANE - MRI	- No statistical difference on clinical outcome scores between groups - No MRI difference in rotator cuff tendon re-tear rate (i.e., 15% in both groups)	Barber et al., 2016 [105]
Arthroscopic rotator cuff repair	n = 17 patients (mean age = 65 years): Tear size (area): 322 ± 180 mm2, L-PRF   n = 18 patients (mean age = 66 years): Tear size (area): 445 ± 421 mm2, No L-PRF	- Blood collection (at 8.30 am.) incitrate tubes - Centrifugation for 12 min with different G-forces: (1) 200× g, (2) 400× g and (3) 1000× g. - Count of platelets, leukocytes and red blood cells in extracted supernatant and “buffy coat” vs normal blood	- Mean follow-up: L-PRF, 14 months; Untreated group, 15 months - SSV, VAS for pain, SST, Constant-Murley	- No complications in either group - No significant differences in clinical outcome, healing rate, mean postoperative defect size, and tendon quality at 12 mo follow-up	Zumstein et al., 2016 [112]
Acute rupture of Achilles tendon	n = 11 patients (mean age = 32.5 ± 3.4 years): PRF augmentation   n = 9 patients (mean age = 34.5 ± 3 years): No PRF   n = 8 patients (mean age = 30 ± 4.4 years): Healthy	- Blood collection in a tube with sodium citrate - Centrifugation (3000 rpm, 10 min)   The protocol included specific jellifying agents (i.e., calcium gluconate and batroxobin)	Follow-up: 6 months - Gait analysis	- % of the stance time of the operated leg, double-support time of the healthy leg, network of the ankle during the gait cycle showed statistically significant differences between the no-PRF and the healthy group - No differences between PRF and healthy groups - Suture + PRF augmentation shows significant functional improvements in motion efficiency	Alviti et al., 2017 [113]
Gluteus medius tendons	n = 18 patients (mean age = 60.26 ± 8.8 years): Tear size: small or low-grade partial tear (33.3%); large or high-grade partial tear (50.0%); large or high-grade full tear (16.7%), PRFM   n = 29 patients (mean age = 63.09 ± 12.0 years): Tear size: small or low-grade partial tear (31.0%); large or high-grade partial tear (58.6%); large or high-grade full tear (10.4%), no PRFM	-	Follow-up: 1 year - Demographic variables	- No effect of PRFM on repair in terms of pain or clinical evidence of retears - PRFM may have a role in improving subjective outcomes of overall and hip-specific physical functioning	Saltzman et al., 2018 [119]

ASES, American Shoulder and Elbow Surgeons, Rowe; ER, external rotation; FF, Forward Flexion; L-PRF, leucocyte- and platelet-rich fibrin; PRFM, Platelet Rich Fibrin Matrix; PRPFM, Platelet Rich Plasma Fibrin Matrix; ROM, Range Of Motion; SANE, Single Assessment Numeric Evaluation; SST, Simple Shoulder Test; SSV, Subjective Shoulder Value; UCLA, University of California, Los Angeles; VAS, Visual Analog Scale; WORC, Western Ontario Rotator Cuff Index.